{"id":"a9d6f4f2-d0cd-52f9-824e-b4cd0ee36f23","stable_key":"b428117d-3a8c-5e74-8711-168153e19545:aspartame-headache-positive","predicate":"increases_reported","statement":"A repeated crossover trial reported headaches on 33% of aspartame days versus 24% of placebo days, P=0.04; 18 of 32 randomized participants completed all periods.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"004417e8-e9a8-57e3-b913-40b87c1b8c8b","mechanism_event_label":"A positive symptom finding comes with substantial missing follow-up.","subject":{"id":"15bd1664-9d4b-514f-ab83-87274a67673f","slug":"aspartame","display_name":"Aspartame","entity_type_key":"small_molecule"},"object":{"id":"33c375a2-59b9-5292-a143-eaca676d6d97","slug":"human-aspartame-headache-frequency","display_name":"Human headache frequency during aspartame challenges","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"004417e8-e9a8-57e3-b913-40b87c1b8c8b","stable_key":"b428117d-3a8c-5e74-8711-168153e19545:aspartame-headache-positive-event","event_type":"observed_relationship","label":"A positive symptom finding comes with substantial missing follow-up.","description":"A repeated crossover trial reported headaches on 33% of aspartame days versus 24% of placebo days, P=0.04; 18 of 32 randomized participants completed all periods.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"15bd1664-9d4b-514f-ab83-87274a67673f","slug":"aspartame","display_name":"Aspartame","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"33c375a2-59b9-5292-a143-eaca676d6d97","slug":"human-aspartame-headache-frequency","display_name":"Human headache frequency during aspartame challenges","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"About 30 mg/kg/day, seven-day periods; self-identified headache-sensitive volunteers.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"No significant difference in headache duration or intensity; attrition and multiple analyses limit certainty.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Aspartame collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"aspartame","display_name":"Aspartame","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A positive symptom finding comes with substantial missing follow-up.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Aspartame ingestion and headaches: a randomized crossover trial. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7936222/ · DOI 10.1212/wnl.44.10.1787","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"7a63a42b-c0c3-5897-ada7-947823712b1d","evidence_kind":"source_excerpt","locator":"Lines 306-312","start_line":306,"end_line":312,"excerpt":"## aspartame-headache-positive\nA positive symptom finding comes with substantial missing follow-up.\nA repeated crossover trial reported headaches on 33% of aspartame days versus 24% of placebo days, P=0.04; 18 of 32 randomized participants completed all periods.\nModel: About 30 mg/kg/day, seven-day periods; self-identified headache-sensitive volunteers.\nLimitations: No significant difference in headache duration or intensity; attrition and multiple analyses limit certainty.\nEvidence access: Primary abstract\nAspartame ingestion and headaches: a randomized crossover trial. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7936222/ · DOI 10.1212/wnl.44.10.1787","model_system":"About 30 mg/kg/day, seven-day periods; self-identified headache-sensitive volunteers.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"2bba7d36-993f-5ba7-acaf-2e4d573527ed","stable_key":"import-b428117d-3a8c-5e74-8711-168153e19545","title":"Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"21cfc6808062c6ea1fb5d34128bcd005d31f0f6c0d63484794238db77d32ae97","revision_id":"1255dda8-df99-5d4b-a65b-4144c47d7d9b","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"d7f1a9f9-d82e-5461-a9ec-e71195cebb78","title":"Aspartame headache challenges: increased frequency versus no increase","kind":"contradiction","status":"open","why":"Two blinded studies in self-reported headache-sensitive adults reached differing conclusions. The repeated trial reported more headache days; the acute trial did not find more headaches. Exposure schedule, selection, attrition and endpoint definition differ and may explain the results, but a common mechanism has not been demonstrated.","resolution":"Unresolved across these protocols. Retain both studies and their limits. Do not label every person sensitive or dismiss reported symptoms. Prospective repeated-dose studies with prespecified endpoints and adequate completion are needed.","created_at":"2026-09-20 04:49:19","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/d7f1a9f9-d82e-5461-a9ec-e71195cebb78","sides":[{"conflict_id":"d7f1a9f9-d82e-5461-a9ec-e71195cebb78","ordinal":0,"label":"Repeated seven-day crossover","revision_id":"1255dda8-df99-5d4b-a65b-4144c47d7d9b","start_line":306,"end_line":312,"quote":"## aspartame-headache-positive\nA positive symptom finding comes with substantial missing follow-up.\nA repeated crossover trial reported headaches on 33% of aspartame days versus 24% of placebo days, P=0.04; 18 of 32 randomized participants completed all periods.\nModel: About 30 mg/kg/day, seven-day periods; self-identified headache-sensitive volunteers.\nLimitations: No significant difference in headache duration or intensity; attrition and multiple analyses limit certainty.\nEvidence access: Primary abstract\nAspartame ingestion and headaches: a randomized crossover trial. · 1994 · https://pubmed.ncbi.nlm.nih.gov/7936222/ · DOI 10.1212/wnl.44.10.1787","source_key":"import-b428117d-3a8c-5e74-8711-168153e19545","source_title":"Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20)","claim_ids":["a9d6f4f2-d0cd-52f9-824e-b4cd0ee36f23"]},{"conflict_id":"d7f1a9f9-d82e-5461-a9ec-e71195cebb78","ordinal":1,"label":"Acute crossover challenge","revision_id":"1255dda8-df99-5d4b-a65b-4144c47d7d9b","start_line":314,"end_line":320,"quote":"## aspartame-headache-null\nAnother blinded study did not reproduce increased headache frequency.\nAn acute crossover challenge in 40 self-reported headache-sensitive adults found headaches in 35% after 30 mg/kg aspartame versus 45% after placebo.\nModel: Acute human challenge.\nLimitations: Different exposure duration from the repeated trial; no molecular mechanism identified.\nEvidence access: Primary abstract\nAspartame and susceptibility to headache. · 1987 · https://pubmed.ncbi.nlm.nih.gov/3657889/ · DOI 10.1056/NEJM198711053171903","source_key":"import-b428117d-3a8c-5e74-8711-168153e19545","source_title":"Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20)","claim_ids":["d6fe1ae6-b104-5a57-8229-3dfd29d464c6"]}]}],"corrections":[],"research":null}